Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Nov;261:744-51.
doi: 10.1016/j.expneurol.2014.08.004. Epub 2014 Aug 10.

Noninvasive Detection of Sleep/Wake Changes and Cataplexy-Like Behaviors in orexin/ataxin-3 Transgenic Narcoleptic Mice Across the Disease Onset

Affiliations
Free PMC article

Noninvasive Detection of Sleep/Wake Changes and Cataplexy-Like Behaviors in orexin/ataxin-3 Transgenic Narcoleptic Mice Across the Disease Onset

Masatoshi Sato et al. Exp Neurol. .
Free PMC article

Abstract

Sleep and behavioral monitoring of young mice is necessary for understating the progress of symptoms in congenital and acquired diseases associated with sleep and movement disorders. In the current study, we have developed a non-invasive sleep monitoring system that identifies wake and sleep patterns of newborn mice using a simple piezoelectric transducer (PZT). Using this system, we have succeeded in detecting age-dependent occurrences and changes in sleep fragmentation of orexin/ataxin-3 narcoleptic mice (a narcoleptic mouse model with postnatal hypocretin/orexin cell death) across the disease onset. We also detected REM sleep/cataplexy patterns (i.e., immobility with clear heartbeat [IMHB] signals due to the flaccid posture) by the PZT system, and found that sudden onset of REM sleep-like episodes specifically occur in narcoleptic, but not in wild type mice, suggesting that these episodes are likely cataplexy. In contrast, gradual onset of IMHB likely reflects occurrence of REM sleep. In summary, we have shown that the PZT system is useful as a non-invasive sleep and behavior monitoring system to analyze the developmental aspects of sleep and movement disorders in mice models.

Keywords: Cataplexy; Disease onset; Hypocretin/orexin; Mice; Narcolepsy; Piezoelectric system; REM sleep.

Figures

Fig. 1
Fig. 1
Piezoelectric transducer (PZT) system. A: Sensor device, B: piezoelectric (PZT) element, C: the main unit, and D: appearance of the cage with a PZT sensor.
Fig. 2
Fig. 2
Piezoelectric (PZT) signals. A: Large amplitude signals appear during movement (wake) while very little amplitude appears during rest (sleep). B: Both (a) ordinary resting (non-IMHB) and (b) IMHB show lower amplitude than movement period but IMHB is characterized by the appearance of heartbeat (heart sound) signals. C: (a) IMHBs: Sudden onset and large movement followed by IMHB. No fewer than 40 s of movement period must exist before IMHBs. (b) IMHBg: Gradual onset IMHB. Fewer than 40 s of movement period before IMHBg.
Fig. 3
Fig. 3
Developmental changes of the amount of sleep and wake in WT and TG narcoleptic mice. There was no significant difference in the sleep and wake amounts between TG narcoleptic and WT mice, nor observed age-dependent changes in these parameters, although modest decreases in sleep amounts and increases in wake amounts were observed in WT in P84 and P98. Amount of sleep: genotype effect (p = 0.076), age effect (p = 0.360), and genotype × age interaction (p = 0.473). Amount of wake: genotype effect (p = 0.316), age effect (p = 0.187), and genotype × age interaction (p = 0.797).
Fig. 4
Fig. 4
Developmental changes of sleep and wake bouts in WT and TG mice. Sleep bout length in TG narcoleptic mice decreased significantly with age (*p < 0.05 for 84 day, **p < 0.01 for 98 day old mice), while no age-dependent change was observed in WT mice. Significant differences in sleep bout length between the genotypes were observed after 84 daysold(p < 0.05 for 84 and 98 day old mice). No significant decline in wake bout length was observed in TG mice. Sleep bouts: genotype effect (p < 0.001), age effect (p = 0.164), and genotype × age interaction (p = 0.243). Wake bouts: genotype effect (p = 0.151), age effect (p = 0.223), and genotype × age interaction (p = 0.999).
Fig. 5
Fig. 5
Frequency distribution of IMHB (total), IMHBs and IMHBg. There was a different distribution between IMHBs and IMHBg, and the duration of the most of IMHBs is short and is less than 56.1 s. Almost all IMHBs were observed in narcoleptic TG mice (TG:WT = 104:1), while IMHBg signals were observed similarly in TG and WT mice (p = 0.131 by K–S test).
Fig. 6
Fig. 6
Developmental changes in the number of appearance of IMHBs. The IMHBs signals were observed as early as 14 days old in TG narcoleptic mice and the frequency of IMHBs increased with age and reached a plateau after 84 days.

Similar articles

See all similar articles

Cited by 2 articles

Publication types

MeSH terms

Feedback